Zinc plays an essential role in cell growth, and is a cofactor of over 300 enzymes, including enzymes important in angiogenesis and cell remodeling. Vallee, B. L., Auld, D. S., Biochem. 29:5647-5659 (1990). Zinc associates with many macromolecules in cells, including molecular components that act to control growth, apoptosis, development and differentiation. Control of intracellular zinc levels, therefore, may be important in preventing the triggering of a variety of disease states, including cancer.
LIV-1 is a member of the LZT (LIV-1-ZIP Zinc Transporters) subfamily of zinc transporter proteins. Taylor, K. M. and Nicholson, R. I., Biochim. Biophys. Acta 1611:16-30 (2003). Computer analysis of the LIV-1 protein reveals a potential metalloprotease motif, fitting the consensus sequence for the catalytic zinc-binding site motif of the zincin metalloprotease.
The structure of LIV-1 implicates a role for the protein as a zinc-influx transporter protein. Experiments with recombinant LIV-1 localizes the protein to the plasma membrane, similarly concentrated in lamellipodiae as membrane-type metalloproteases. Taylor and Nicholson, supra. Computer analysis predicts six to eight transmembrane domains, a long extracellular N terminus, a short extracellular C terminus, as well as the consensus sequence for the catalytic zinc-binding site of metalloproteases. LIV-1 distribution studies indicates primary expression in breast, prostate, pituitary gland and brain tissue. Taylor and Nicholson, supra.
The LIV-1 protein has also been implicated in certain cancerous conditions, e.g. breast cancer and prostate cancer. The detection of LIV-1 is associated with estrogen receptor-positive breast cancer, McClelland, R. A., et al., Br. J. Cancer 77:1653-1656 (1998), and the metastatic spread of these cancers to the regional lymph nodes. Manning, D. A. et al., Eur. J. Cancer 30A:675-678 (1994). Antibodies useful for diagnosis, prognosis, and effective treatment of cancer, including metastatic cancer, would be desirable. Accordingly, provided herein are compositions and methods that can be used in diagnosis, prognosis, and therapy of certain cancers.